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Content Provider | IEEE Xplore Digital Library |
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Author | Stroh, M.A. Saltzman, W.M. |
Copyright Year | 2002 |
Description | Author affiliation: Dept. of Chem. Eng., Cornell Univ., Ithaca, NY, USA (Stroh, M.A.; Saltzman, W.M.) |
Abstract | By understanding how neurotrophins navigate through brain tissue, we move closer to unlocking the potential therapeutic benefit of these small (26-28kD), basic proteins. We utilize two-photon laser scanning microscopy (TPLSM) to characterize the temporal and spatial fate of the prototypical neurotrophin, nerve growth factor, in brain tissue. We administer a rhodamine-nerve growth factor conjugate (RNGF) from a micropipette to the striatal region of rat brain tissue slices. Two-photon imaging allows us to image deep into 400 micron-thick tissue slices with minimal photodamage of tissue and photobleaching of label. We use a point-source diffusion model to describe the distribution of RNGF and estimate an apparent brain tissue diffusion coefficient (D/sub B/(34/spl deg/C)) of 2.75/spl times/10/sup -7/cm/sup 2//sec. We utilize two-photon fluorescence photobleaching recovery (FPR) to estimate the free diffusion coefficient in water (D/sub F/(34/spl deg/C)) of 8.79/spl times/10/sup -7/cm/sup 2//sec. The extracellular space creates a tortuous path for diffusion, and an anticipated mismatch between D/sub F/ and D/sub B/. The square-root of the ratio of D/sub F/ to D/sub B/ gives the tortuosity, /spl tau/. We compare our estimate of /spl tau/ (1.79) to literature values for other proteins, and conclude that NGF enjoys relatively rapid diffusion in tissue. We extrapolate these findings to postulate formulation strategies for eventual clinical application. |
Starting Page | 518 |
Ending Page | 519 |
File Size | 181407 |
Page Count | 2 |
File Format | |
ISBN | 0780376129 |
ISSN | 1094687X |
DOI | 10.1109/IEMBS.2002.1136926 |
Language | English |
Publisher | Institute of Electrical and Electronics Engineers, Inc. (IEEE) |
Publisher Date | 2002-10-23 |
Publisher Place | USA |
Access Restriction | Subscribed |
Rights Holder | Institute of Electrical and Electronics Engineers, Inc. (IEEE) |
Subject Keyword | Brain Photobleaching Fluorescence Navigation Microscopy Extracellular Chemical engineering Protein engineering Chemical lasers Prototypes |
Content Type | Text |
Resource Type | Article |
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